Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 11 to 12 Months (V419-008)

Bacterial Infections Clinical Trial

Official title:

A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 11 to 12 Months

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01480258
• Other study ID #: V419-008
• Secondary ID: 2010-021491-28V4
• Status: Completed
• Phase: Phase 3
• Start date: November 23, 2011
• Est. completion date: October 9, 2013

Study information

• Verified date: March 2019
• Source: MCM Vaccines B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine whether participants who receive V419 (PR5I) at 2, 4, and 11 to 12 months of age have an acceptable response to the vaccine. This study will also determine whether the immune response to V419 is similar to that of participants who received a licensed vaccine control. The primary hypothesis is that participants who receive PR5I at 2, 4, and 11 to 12 months have an acceptable response rate to all PR5I-contained antigens at one month after the Toddler dose of PR5I.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1315
• Est. completion date: October 9, 2013
• Est. primary completion date: October 9, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 46 Days to 89 Days

Eligibility

Inclusion Criteria:

• Healthy infant able to attend all study visits

• Parent(s)/legal representative are able to read, understand, and complete study questionnaires

Exclusion Criteria:

• History of congenital or acquired immunodeficiency

• Received or is expected to receive immunosuppressive agents or systemic immunomodulatory steroids

• History of leukemia, lymphoma, malignant melanoma, or myeloproliferative disorder

• Hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines or concomitant study vaccines

• Has any chronic illness that could interfere with study conduct or completion

• Received any immune globulin, blood, or blood-derived products since birth

• Received a dose of hepatitis B vaccine prior to study entry

• Vaccinated with any acellular pertussis or whole cell pertussis based combination vaccines, Haemophilus influenzae type b conjugate, poliovirus, pneumococcal conjugate or pneumococcal polysaccharide, rotavirus vaccine, or combination thereof

• Fever within 24 hours prior to enrollment

• Received any non-study vaccine within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 14 days or more prior to enrolment

• Has a coagulation disorder

• Has developmental delay or neurological disorder

• Participant or his/her mother has a medical history of hepatitis B surface antigens (HBsAg) seropositivity

• History of Haemophilus influenzae type b, hepatitis B, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus gastroenteritis, or invasive pneumococcal infection

Related Conditions & MeSH terms

• Bacterial Infections
• Virus Diseases

Intervention

Biological:
• PR5I
DTaP-HB-IPV-Hib (Diphtheria, tetanus, pertussis [acellular, component], hepatitis B [recombinant DNA], polio virus [inactivated], and Haemophilus influenza type b conjugate vaccine [adsorbed]) Vaccine 0.5 mL intramuscular injection at 2, 4, and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. PR5I is a liquid suspension hexavalent vaccine.
• Rotavirus vaccine
Rotarix™ 1.5 mL oral dose at 2 and 4 months of age (subset 1, Italy and Sweden) or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age (subset 2, Finland)
• Prevenar 13™
Prevenar 13™ 0.5 mL intramuscular injection at 2, 4, and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine.
• INFANRIX™ hexa
Combined Diphtheria-Tetanus-acellular Pertussis [DTaP], Hepatitis B [HepB], Poliovirus [IPV] and Haemophilus influenzae type b [Hib] Vaccine 0.5 mL intramuscular injection at 2, 4 and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. INFANRIX™ hexa is provided as 2 components (lyophilized Hib and liquid DTaP, IPV, and HepB). Prior to administration, the vaccine must be reconstituted by adding the liquid DTaP-HepB-IPV component to the vial containing the Hib pellet.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
MCM Vaccines B.V.	Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age)	Acceptability response rates were defined as Ab titre =1.0 µg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); =10 mIU/mL for Hepatitis (HBsAg); =0.1 IU/mL for diphtheria and tetanus; =8 (1/dil) for inactive poliovirus type (IPV) 1, 2 & 3, and percentage of pertussis seroresponder participants (Pertussis toxoid [PT], Filamentous haemagglutinin [FHA], Fimbriae types 2 & 3 [FIM] and Pertactin [PRN]) 1 month Post-Toddler dose of PR5I. Seroresponse was defined: (1) If pre-Dose 1 Ab concentration (cc) was	1 month after Toddler dose of PR51 (post-toddler dose)
Secondary	Non-inferiority of Antibody (Ab) Response Rate to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa	Percentage of participants with an Ab titre =1.0 µg/mL for Hib (polyribosylribitol phosphate, PRP) measured by radioimmunoassay (RIA) 1 month post-infant dose 2 of PR5I or INFANRIX hexa.	1 month after the 2nd dose (post-infant dose 2)
Secondary	Superiority of Antibody (Ab) Response Rates to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa	Percentage of participants with an Ab titre =1.0 µg/mL for Hib (polyribosylribitol phosphate, PRP) measured by RIA 1 month post-infant dose 2 of PR5I or INFANRIX hexa.	1 month after the 2nd dose (post-infant dose 2)
Secondary	Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa	Percentage of participants with pre-specified Ab titre for PRP, HBsAg, diphtheria, tetanus, IPV1, 2 & 3, and percentage of pertussis seroresponder participants (PT, FHA, FIM and PRN) 1 month post-toddler dose were calculated based on the method by Miettinen and Nurminen stratified by country. Seroresponse was defined: (1) If pre-Dose 1 Ab cc was	1 month after Toddler dose (post-toddler dose)
Secondary	Non-inferiority of Rotavirus Response (Geometric Mean Titer, GMT) One Month After the 2nd Dose of Rotarix (4 Months of Age) Administered Concomitantly With PR5I Versus INFANRIX Hexa	Antibody titres expressed in units/mL were measured for Rotavirus IgA by Enzyme Immunoassay (EIA), 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2). The 95% CI for GMT was based on the t-distribution of the natural log-transformed antibody titer.	1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2)
Secondary	Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination	Injection-site and systemic AEs were reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 (D1) to D15 after each vaccination. Solicited injection site and systemic AEs were reported daily from D1 to D5 after each vaccination. AEs at injection sites were always considered as vaccine-related (V-related) (Injection-Site Reactions [ISRs]). The investigator had to assess whether systemic AEs were related or not to the vaccine. All AEs (related and unrelated) are displayed here.	Solicited AEs: up to 5 days (Days 1-5 after any vaccination); unsolicited AEs: up to 15 days (Day 1-15 after any vaccination)
Secondary	Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination	Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions [ISRs]). Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from D1 to D5 after vaccination.	Up to 5 days (Day 1 to Day 5 following vaccination)
Secondary	Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination	Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions {ISRs]). Unsolicited ISRs occurring from Day 1 (D1) to D15 after any vaccination were reported daily on the VRC by the parent(s) or legal representative. Unsolicited ISRs with incidence =1% are reported below.	From D1 to D15 after any vaccination
Secondary	Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination	Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature =38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator had to assess whether these systemic AEs were related or not to the vaccines. All (related and unrelated) are displayed here.	Up to 5 days (from D1 to D5 after any vaccination)